The present invention relates to hexahydrobenzo[f]quinolinones, pharmaceutical formulations containing those compounds and their use as steroid 5.alpha.-reductase inhibitors.
It is generally known that certain undesirable physiological conditions such as benign prostatic hyperplasia, male pattern baldness, acne vulgaris, hirsutism and prostatic cancer are androgen mediated conditions dependent on 5.alpha.-dihydrotestosterone (DHT).
The enzyme 5.alpha.-reductase mediates the conversion of testosterone to the more potent androgen DHT locally, in the target organ. It has been postulated, and demonstrated, that inhibitors of 5.alpha.-reductase should block the formation of DHT and bring about amelioration of the above undesirable physiological conditions.
Compounds reportedly useful for inhibiting 5.alpha.-reductase are generally steroid derivatives such as the azasteroids in Rasmusson, et al., J. Med. Chem., 29, (11), 2298-2315 (1986); and benzoylaminophenoxy-butanoic acid derivatives such as those disclosed in EPO 291 245.
Certain hexahydrobenzo[f]quinolinone compounds are known. See, for example, GB 2,207,135; and U.S. Pat. No. 4,749,791. Both GB 2,207,135 and U.S. Pat. No. 4,749,791 do not disclose a pharmaceutical use for the hexahydrobenzo[f]quinolinones disclosed therein except as intermediates for the preparation of other compounds said to have pharmaceutical utility. U.S. Pat. No. 4,511,569 discloses that certain tricyclic lactams and derivatives are useful in increasing cardiac contractility. The references do not suggest the hexahydrobenzo[f]quinolinones of the present invention would be useful as steroid 5.alpha.-reductase inhibitors.
Accordingly, it is one object of the present invention to provide novel hexahydrobenzo[f]quinolinones which are potent selective steroid-5.alpha.-reductase inhibitors useful in the treatment of benign prostatic hyperplasia, male pattern baldness, acne vulgaris, hirsutism and prostatic cancer.
A further object of the present invention is to provide therapeutic compositions for treating said conditions.
Still another object is to provide methods for treating said conditions.
Other objects, features and advantages will become apparent to those skilled in the art from the following description and claims.